Dr. Raju R SahetyaM.D., D.G.O., D.F.P., F.C.P.S., F.I.C.O.G.,

OBSTETRICIAN & GYNAECOLOGISTSpecialist: Infertility & Maternal Fetal Medicine

HospitalPushpaa Hospital

Mumbai, India

www.pushpaahospital.com, drrajusahetya@gmail.com

Mobile 9821090102

HonoraryHinduja Hospital * BSES Hospital

Mumbadevi Hospital * Hiranandani Hospita

Vice PresidentIndian Society for Prenatal Diagnosis & Fetal Therapy (ISPAT)

Member Excecutive CouncilMumbai Obstetrics & Gynaecology Society (MOGS)

Association of Fellow Gynaecologist (AFG)Assciation of Medical Consultant (AMC)

Current Position Held

MOGS – PNDT & Academic Cell, FOGSI – Sexual Medicine Committee

Editorial Board – ISPAT International Journal of Prenatal Diagnosis & AFG Times

Rotarian Past President Rotary Club of Bombay Airport

“I OWE TO MY ALMA MATER !”

possible causes

Recurrent miscarriage is a heterogeneous condition that has many possible causes; more than one contributory factor may underlie the recurrent pregnancy losses.

each Loss may have had a different or multiple causes.

Geneticfactors

Anatomicalfactors

EndocrineInfective

agents

Immunefactors

InheretedThrombophilic

defect

Explained Un-explained

RecurentMiscarriage

Enviromentalfactors

Body Cervix

Paternalkaryotyping

CytogeneticOf miscarriage

C I

Uterineanomalies

APS

BacterialVaginosis

50 % of all conception are lost (includes early abortions).

15-20 % of recognized pregnancies.

70% of these early losses is due to cytogenetic

50% between 8-15 weeks.

5 – 10 % still births.

Pregnancy Loss

Chromosomal Mendelian Inheritance.

Multifactorial.

Establish the etiology

Investigate the couple

Estimate recurrence risk

Provide accurate genetic counseling.

Discuss reproductive options.

Essential as patients have small planned families.

Denovo, paternal or maternal meiotic or post zygotic division or abnormal fertilization.

26 % are trisomies including trisomy 16.

10 % are triploidy , tetraploidy.

10 % are sex chromosomal monosomy (45,X)

2% are unbalanced or double trisomies.

.?9% trisomy and still birth Histopathology / morphology insufficient to asses etiology.

•Tissues usually used for karyotype from abortuses.

Chorionic Villi from products in normal saline

Piece of placenta at cord insertion in normal saline.

Fetal cord / cardiac blood, in sodium heparin vaccutainers.

• No formalin or freezing for preservation

• Should reach within 24-36 hours at Room Temperature. 

NABL ACCREDITED (ISO / IEC – 17025)

AccreditationsExperienced Medical GeneticistQualified staff

State of the art equipment.Reliable reports Minimum turn around time.Interaction with physician.

Accessibility

History taking.

Genetic counseling

Examination of the Fetus, Villi and Placenta. Correlation with CRL and stage ( milestones)

Morphology of the villi. (hydropic, hypoplastic etc.)

Review of Ultrasound reports .(Syndrome assignment.)

Photography and / or Radiology (skeletal dysplasias)

Karyotype studies and FISH for fetal chromosomal abnormalities.

Histopathology studies for infection and vascular insufficiency.

Karyotype of the couple - for transmissible chromosomal error.

Prenatal Genetic Diagnosis in subsequent pregnancy

Medical and Maternal

Family

Previous and present pregnancy.

Antenatal

Fetal wellbeing

Labor and Postnatal.

Level 1 – Obstetrician

Discussing causes for Pregnancy Loss

Investigations required

Role of Geneticist

Level 2 – Clinical Geneticist

Details about causes in RPL

To evaluate, Diagnose and Prognosis

Discuss recurrences

C

E

MORPHOLOGY & KARYOTYPE OF VILLI

NORMAL-46,XX/46,XY

CLUBBING- VARIABLE

-

- MOLAR- 46,XX / 46,XY

HYPOPLASTIC- 45,XO

CYSTIC- 69,XXX/XXYTRI-16

Exomphalos. Trisomy 18.

Holoprosencephaly Trisomy13, 15.

Choroid Plexus Cyst Trisomy 18.

Nuchal Translucency Trisomy 21.45X.

Ventriculomegaly 13,18,21

Cystic Hygroma45X.

Trisomy 18

Monosomy XTriploidy Trisomy 13

Trisomy 21

FISH (Fluroscent Insitu Hybridization)

Permits detection of specific nucleic acid sequences in morphologically preserved chromosomes, cells, and tissues.

Specific probes are utilized for the purpose.

Karyotype FISHNeeds viable ,specific tissues

Any fetal tissue either fresh, frozen or paraffin block

Culture essential Uncultured cells work.

Selective growth of maternal decidua

Not possible.

Screens all chromosomes and used for > 40 yrs now for establishing etiology.

Screens for major aneuploidies (13, 18, 21, X and Y)

Turn around time 2 weeks Turn around time 2 days Ideal for focal anomalies

DEPENDS ON :

• Parental age . Advanced maternal age : Trisomic conceptus Monosomy X.

• Cytogenetic status of the spontaneous abortion. Exponential increase in the rate of trisomy

• Karyotype of parents (balanced translocations).Leads to deficiencies and duplication of chromosomes in the fetus

Parental Karyotype.

Prenatal Diagnosis PGD / CVS / Amniocentesis

Gamet Donation.

CHORIONIC VILLUS SAMPLING10-11 WEEKS

AMNIOCENTESIS 15-17 WEEKS

Frequency : 2-3 per 1000.

Inheritance : Multifactorial, single gene / chromosomal.

Recurrence risk : 9% / 2-3%.

Periconceptional folic acid supplement.

Neural Tube Defects

Genetic Factors more often responsible for RPL

Genetic Counseling plays an important role in RPL management.

Cytogenetic/FISH and morphological evaluation of products of conception is a valuable tool for assessing a cause of fetal loss.

Prenatal Genetic Diagnosis in subsequent pregnancy